QTc-interval prolongation and increased risk of sudden cardiac death associated with hydroxychloroquine

Abstract

Aims: Hydroxychloroquine and chloroquine ([hydroxy]chloroquine) are drugs used to treat malaria and rheumatological disorders and were recently suggested as beneficial for prevention and treatment of patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. However, longitudinal studies to assess the electrocardiographic and cardiotoxic effects of these drugs are limited. In this study, we aimed to investigate the effect of these drugs on QTc-interval and incidence of sudden cardiac death (SCD). Methods We designed a longitudinal follow-up study of individuals within the prospective population-based Rotterdam Study. Eligible individuals had available data on medication and repeated ECG measurements. The study period was between 1 January 1991 and 1 January 2014. We studied on current and past use of [hydroxy]chloroquine as a time-varying exposure; high versus low daily dose of [hydroxy]chloroquine. QTc-interval duration, and the occurrence of SCD were the main outcomes. SCD was defined as an unexpected and sudden death due to cardiac arrhythmia within one hour of the onset of acute symptoms, and in patients without cardiac symptoms within 24 hours before death. Results Among the study population of 14 594 individuals (58.8% women) with an average age of 65 years, 346 patients used [hydroxy]chloroquine at any time during follow-up. The total number of SCD cases was 609. In a multiple linear mixed model analysis, the current use of [hydroxy]chloroquine was associated with a significantly increased duration of the QTc-interval of 8.1 ms (95% CI: 3.6; 12.6) compared with non-users. The association was stronger among current-high daily dosage [15.3 (95%CI: 7.0; 23.6)] compared with current-low daily dosage [5.5 (95%CI: 0.4; 10.7)] users. In a Cox proportional hazard regression analysis, the risk of SCD was significantly higher in participants who were current users of [hydroxy]chloroquine than in non-users [adjusted hazard ratio; 3.7 (95%CI: 1.1; 12.6)]. Conclusions In this longitudinal study, persons who received [hydroxy]chloroquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.

Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine

“…These include expression of the B cell activation marker CD71, an iron transport receptor that is commonly expressed on antigen-specific B cell subsets including in the context of vaccination (53,54). Reports of CD71 expression after COVID-19 infection (55,56) are consistent with overlap of mRNA vaccination and natural SARS-CoV-2 infection. Limited pre-existing immunity to endemic coronaviruses prior to SARS-CoV-2 vaccination was detected in this study, albeit at varying levels between donors.…”

Using Mendelian randomization to unveil the truth: does COVID-19 impact QT interval prolongation?

“…Furthermore, the association between COVID-19 and QT interval prolongation may involve undiscovered genetic or environmental factors. Notably, certain existing drugs, such as chloroquine and lopinavir, have been widely discussed for their potential to cause QT prolongation when used in COVID-19 treatment [43][44][45][46][47][48][49][50] . These drugs, however, had previously been reported to cause QT prolongation by targeting the K V11.1 potassium channel even before the emergence of COVID-19 and untreated COVID-19 patients also exhibited QT interval prolongation 4,14,43,51 .…”

Hyper/neuroinflammation in COVID-19 and suicide etiopathogenesis: Hypothesis for a nefarious collision?

“…However, some associations between suicide risk and anti-inflammatory therapies have been reported. In this regard, the controversial usage of the anti-malarial drug, hydroxychloroquine, in COVID-19 patients has been linked to significant cardiotoxicity and other neuropsychiatric complications, including suicide ( Ahmadizar et al, 2020 , Boulware et al, 2020 , Cavalcanti et al, 2020 , Hamm and Rosenthal, 2020 , Ong et al, 2021 ). In light of this clinical experience, possible risk of suicide must be carefully examined for all anti-inflammatory therapies, in the context of suicide prevention for COVID-19 survivors.…”